Blood vessels and naturally occurring internal organs are lined with a thin layer of endothelial cells which have a number of bio-chemical functions. In so far as surgical implants are concerned, one important function of endothelial cells is their involvement in the processes of rendering the surfaces of blood vessels non-thrombogenic.
A key factor in attaining a non-thrombogenic vascular graft is the rapid development of a lining of the endothelial cells on the implant. Thus, such implants benefit from having surfaces that encourage endothelial cell attachment and spreading.
Similar considerations apply in respect of other implants that are intended for prolonged implantation where blood contact is required such as permanent indwelling catheters for drug administration, fluid drainage tubes, vascular shunts, pacemaker leads and implantable transducers.
Synthetic polymer hydrogels have found a wide range of biomedical applications, including controlled drug delivery systems, replacement blood vessels, would dressings, coatings for biosensors, soft tissue substitution and contact lenses.
As a family of polymeric materials, synthetic hydrogels are generally well tolerated when implanted in vivo and can be tailored to suit the many potential functions of prosthetic devices in contact with blood or soft tissues. The success of hydrogels as biomaterials lies partially in their superficial resemblance to living tissue, a property attributable to their relatively high water content (say 20%-99%), which immediately results in minimal frictional irritation of surrounding tissues.
In addition, hydrogels can be non-toxic, chemically stable and (due to their water content) can exhibit a low interfacial tension with aqueous environments. This latter property becomes particularly important in considering the compatibility of blood-contacting surfaces, where minimal interfacial tension has been related to thromboresistance.
The hydrogel polyHEMA--poly(2-hydroxyethyl methacrylate)--is known to possess inherent characteristics of good permeability, water uptake and tolerable polymer/tissue interface disruption which make it a desirable biomaterial (see, for example, Cohn D et al (1984) Radiation--Grafted Polymers for Biomaterial Applications I. 2-Hydroxyethyl Methacrylate: Ethyl Methacrylate Grafting on to Low Density Polyethylene Films J. App. Pol. Sci. 29, 2645-2663).
Despite these advantages, however, unmodified polyHEMA does not have the ability to sustain mammalian cell growth and consequently its use as a biomaterial has been restricted to applications where this inability is a positive advantage (see Andrade J. D. (1975) Hydrogels for Medical and Related Applications ACS SYMPOSIUM SERIES 31, Washington).
Recent investigations into the effects of treating polystyrene with sulphuric acid (see Curtis A.S.G. et al (1983) Adhesion of Cells to Polystyrene Surfaces J. Cell Biol 97, 1500-1506) have shown a marked improvement in the ability of that polymer to support mammalian cell growth after acid etching. Whilst this is not a new concept, modern analytical methods such as electron spectroscopy for chemical analysis have allowed a more detailed study of surface changes occurring with such treatments resulting in some clarification of certain aspects of cell adhesion.
Another disadvantage of polyHEMA is that its poor mechanical properties prevent it from being used as an implant requiring high mechanical strength.
By copolymerisation of polyHEMA with other selected synthetic polymers, it has been possible to manipulate surface charges, hydrophilicity and equilibrium water content to achieve varying degrees of attachment and growth of fibroblastoid cells. An alternative modification has been to incorporate natural polymers such as collagen, elastin and fibronectin in polyHEMA hydrogels. This has provided a model system to study the contribution of such extracellular matrix components to cell adhesion and growth. While this approach has allowed the growth of a wider variety of cell types on such hydrogels, it also places other restrictions and problems on the polyHEMA system as a biomaterial for use in prosthetic devices.
It is an object of this invention to provide an implantable material having improved biocompatibility arriving from enhanced endothelial cell attachment properties.
It is a further object of this invention to provide an improved implantable material having a mechanically acceptable substrate to which is attached a polyHEMA layer.